Local Study Finds New Evidence Supporting a Genetic Link to Obesity

From Michelle Obama’s crusade against boxed mac and cheese to the cult followings of The Biggest Loser and other weight loss reality shows, it’s no secret that America is dealing with an obesity crisis. Current CDC figures show that more than one-third of adults in the U.S. are obese, and the World Health Organization reports that global rates of obesity have more than doubled since 1980.

While the connection between obesity and lifestyle factors such as diet and exercise has been well documented, less is known about the role of genetics. That’s where the Genetic Investigation of Anthropometric Traits (GIANT) Consortium comes in.

In companion studies published earlier this month in the journal Nature, researchers from the international organization—which includes local scientists from Harvard Medical School (HMS), Boston Children’s Hospital, and the Broad Institute at MIT and Harvard—discovered more than 140 locations in the human genome that influence obesity. It is the largest study on genetic variation in obesity ever conducted, according to an HMS report.

Joel Hirschhorn, one of the study’s contributing authors and an associate professor of genetics at HMS and Boston Children’s, says that this latest discovery on the genetic link to obesity has been about four years in the making. Using new computational methods, researchers combed through genetic samples from more than 300,000 participants to find areas in the genome that relate to body mass index (BMI) and waist-hip ratio—two significant metrics of obesity. Hirschhorn says that identifying these areas in the genome will help researchers understand the underlying biology of obesity, which may lead to the development of more effective therapies and treatments in the future.

“We have some general things that we say in terms of diet and exercise to try to treat obesity, but we know that those are very hard to sustain,” Hirschhorn says. “The drugs that we have either have a lot of side effects or don’t work that well. The last treatment we have is bariatric surgery, which obviously works but it’s very invasive. We feel that much better treatments are needed but we don’t really understand the biology, and if we don’t understand the biology we’re kind of shooting in the dark.”

In addition to identifying new areas in the genome, researchers learned that the biology behind the two obesity metrics is quite different. Hirschhorn says the study revealed that BMI is related to the brain, while waist-hip ratio—which examines how the body distributes fat—actually has more to do with fat cells and hormone levels. He says that he hopes these findings will not only lead to better interventions, but will inspire other scientists to conduct further research in this area.

“This is the first time we’ve been able to point to something that you could sink your teeth into a little bit. We’re going to continue to do these genetic studies and look at different types of genetic variants, and we’re hoping that will give us better views.” Hirschhorn says. “Right now we feel like we’ve just gotten to look through a tiny keyhole at this exciting room beyond. We’d like to open the door to get a much better look at the biology.”